Associations of plasma homocysteine and the methylenetetrahydrofolate reductase C677T polymorphism with carotid intima media thickness among South Asian, Chinese and European Canadians

Kelemen, Linda E.; Anand, Sonia S.; Hegele, Robert A.; Stampfer, Meir J.; Rosner, Bernard; Willett, Walter C.; Montague, Patricia A.; Lonn, Eva; Vuksan, Vladimir; Teo, Koon K.; Devanesen, Sudarshan; Yusuf, Salim

doi:10.1016/j.atherosclerosis.2004.06.003

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Volume 176, Issue 2 , Pages 361-370, October 2004

Associations of plasma homocysteine and the methylenetetrahydrofolate reductase C677T polymorphism with carotid intima media thickness among South Asian, Chinese and European Canadians

Linda E. Kelemen
- Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, USA
- Corresponding author.
Sonia S. Anand
- Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ont., Canada
- Department of Medicine, McMaster University, Hamilton, Ont., Canada
Robert A. Hegele
- Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, London, Ont., Canada
Meir J. Stampfer
- Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, MA, USA
- Department of Medicine, Channing Laboratory, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
Bernard Rosner
- Department of Medicine, Channing Laboratory, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
Walter C. Willett
- Departments of Epidemiology and Nutrition, Harvard School of Public Health, Boston, MA, USA
- Department of Medicine, Channing Laboratory, Harvard Medical School, Brigham and Women’s Hospital, Boston, MA, USA
Patricia A. Montague
- Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ont., Canada
- Department of Medicine, McMaster University, Hamilton, Ont., Canada
Eva Lonn
- Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ont., Canada
- Department of Medicine, McMaster University, Hamilton, Ont., Canada
Vladimir Vuksan
- Clinical Nutrition and Risk Factor Modification Centre, St. Michael’s Hospital, Toronto, Ont., Canada
- Faculty of Medicine, University of Toronto, Toronto, Ont., Canada
Koon K. Teo
- Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ont., Canada
- Department of Medicine, McMaster University, Hamilton, Ont., Canada
Sudarshan Devanesen
- Faculty of Medicine, University of Toronto, Toronto, Ont., Canada
Salim Yusuf
- Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ont., Canada
- Department of Medicine, McMaster University, Hamilton, Ont., Canada
- for the SHARE Investigators.

Received 1 December 2003; received in revised form 13 May 2004; accepted 1 June 2004.

Abstract

Background: Few studies have evaluated the associations of plasma homocysteine concentration, the methylenetetrahydrofolate reductase (MTHFR) C677T genotype and B vitamin concentration with intima media thickness (IMT) in multiethnic populations. Methods: In the Study of Health Assessment and Risk in Ethnic groups (SHARE), we measured carotid IMT, fasting serum folate, serum B12, plasma pyridoxal-5′-phosphate (PLP) and plasma homocysteine and determined the MTHFR C677T genotype in a cross-sectional study of 818 South Asian, Chinese and European Canadians without previous history of CVD, cancer or diabetes during 1996–1998. Results: Plasma homocysteine was inversely related to serum folate, serum B12, plasma PLP, B vitamin supplement use and Chinese ethnicity, and was positively associated with hypertension, smoking, IMT, MTHFR 677T/T genotype and South Asian ethnicity. Although ethnicity was not a statistically significant modifier, among carriers of the MTHFR 677T/T genotype with serum folate ≤14nmol/L compared to >14nmol/L, plasma homocysteine was significantly higher among South Asians (50.9% increase, P < 0.001) and Europeans (52.4% increase, P < 0.001) but not Chinese (11.0% increase, P > 0.05). Plasma homocysteine > 11.7μmol/L was associated with a 5.9% (95% CI: 1.9%, 10.0%) increase in IMT (approximately 0.04mm) in the pooled-data analyses with similar increases noted in the ethnic-specific analyses. The 677T/T genotype was not associated with a significant change in IMT in the pooled-data analyses (2.7%; 95% CI: −1.7%, 7.2%) nor in ethnic-specific analyses compared to other genotypes, although there were only 63 677T/T homozygotes. Conclusion: The combination of lower serum folate and the MTHFR 677T/T genotype is associated with increased plasma homocysteine among South Asians and Europeans, but the association is not evident among Chinese possibly because their serum folate may not have been low enough to compromise MTHFR activity. Plasma homocysteine > 11.7μmol/L appears to be associated with a clinically important increase in IMT.